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Erythrocyte surface proteins have been identified as receptors of Plasmodium falciparum merozoite proteins. The ligand-receptor interactions enable the parasite to invade human erythrocytes, initiating the clinical symptoms of malaria. These interactions are likely to have had an evolutionary impact on the genes that encode the ligand and receptor proteins. We used sequence data from Kilifi, Kenya to detect departures from neutrality in a paired analysis of P. falciparum merozoite ligands and their erythrocyte receptor genes from the same population. We genotyped parasite and human DNA obtained from 93 individuals with severe malaria. We examined six merozoite ligands EBA175, EBL1, EBA140, MSP1, Rh4 and Rh5, and their corresponding erythrocyte receptors, glycophorin (Gyp) A, GypB, GypC, band 3, complement receptor (CR) 1 and basigin, focusing on the regions involved in the ligand-receptor interactions. Positive Tajima's D values (>1) were observed only in the MSP1 C-terminal region and EBA175 region II, while negative values (1). Both these genes contain multiple polymorphisms, which in the case of EBA175 may counteract receptor polymorphisms and/or evade host immune responses and in MSP1 the polymorphisms may primarily evade host immune responses.

Original publication

DOI

10.1016/j.meegid.2019.02.004

Type

Journal

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases

Publication Date

04/2019

Volume

69

Pages

235 - 245

Addresses

KEMRI-Wellcome Trust Collaborative Programme, P.O. Box 230, 80108 Kilifi, Kenya; Centre for Biotechnology and Bioinformatics, College of Biological and Physical Sciences, Chiromo Campus, University of Nairobi, P. O. Box 30197, Nairobi, Kenya. Electronic address: liochola@kemri-wellcome.org.

Keywords

Erythrocytes, Humans, Plasmodium falciparum, Malaria, Falciparum, Receptors, Cell Surface, Protozoan Proteins, Ligands, Protein Conformation, Structure-Activity Relationship, Gene Frequency, Polymorphism, Genetic, Alleles, Models, Molecular, Child, Child, Preschool, Infant, Infant, Newborn, Female, Male, Merozoites, Host-Parasite Interactions